Recent years have witnessed a dramatic upsurge in awareness among chemists of the potential utility of asymmetric organocatalysis as a tool for the synthesis of enantiopure molecules under mild and environmentally benign conditions. The Michael addition of 1,3-dicarbonyl nucleophiles to nitroolefins 2 provides a particularly attractive target for organocatalyst design, largely due to the ready availability and high reactivity of nitroalkenes and the ability of the nitro functionality to accept hydrogen bonds from suitably designed catalyst systems, especially for the synthesis of important nitrogen containing bioactive agrochemical and pharmaceutical compounds. Thus, reactions of this nature have been reported to proceed in high yield and with good enantioselectivity by the use of various asymmetric catalysts. In contrast, organocatalytic conjugated additions using aromatic ketones as the Michael donor are rarely studied. 1,3-Diphenyl-1,3-propanedione (1a) is for instance known not to be a good Michael donor due to the steric hindrance of the two aryl groups and generally requires harsh reaction conditions and long reaction times.
The development of a highly enantioselective recyclable strategy (Dioumaev, V. K., & Bullock, R. M., Nature (2003) 424, 530; Ishihara, K., et al., Synlett (2002) 1299) for organocatalysis remains a challenging task. A few recyclable processes have been designed to this day, by attaching the catalyst to polymers (Font, D., et al., Org. Lett. (2006) 8, 4653; Font, D., et al., Org. Lett. (2007) 9, 1943), using recyclable fluorous catalysts (Huang, K., et al., Org. Chem. (2006) 71, 8320; Cole, A., et al., J. Am. Chem. Soc. (2002) 124, 5962; Luo, S., et al., Angew. Chem., Int. Ed. (2006) 45, 3093) and ionic liquids (Yao, Q., & Zhang, Y., J. Am. Chem. Soc. (2004) 126, 74; Dalicsek, Z., et al., Org. Lett. (2005) 7, 3243; Zu, L., et al., Org. Lett. (2006) 8, 307; Chowdari, N. S., et al., Synlett (2003) 1906). However, only moderate results have been achieved so far.
Accordingly, it is an object of the present invention to provide a process of carrying out a Michael reaction in which the catalyst can be recycled.